crossing96/oncoscreening huggingface dataset:
NOS3 895G&gt;T and CBR3 730G&gt;A Are Associated with Recurrence Risk in Non-Muscle-Invasive Bladder Cancer with Intravesical Instillations of THP.	OBJECTIVES: To analyze the correlation between pharmacogenomic biomarkers and the efficacy of pirarubicin (THP, also named 4'-O-tetrahydropyranyl-adriamycin) and to explore potential associations of individual genetic backgrounds with the clinical outcomes of non-muscle-invasive bladder cancer (NMIBC) patients. METHODS: Between July 2003 and June 2011, a total of 91 patients were treated with transurethral resection (TUR) of the bladder tumor and were histopathologically confirmed to have NMIBC. Patients received an immediate instillation and maintenance therapy with THP. All patients underwent follow-up for recurrence. We genotyped 13 single nucleotide polymorphisms (SNPs) from blood and saliva DNA samples of all patients. RESULTS: The associations of patients' genotypes with tumor recurrence risks were analyzed by survival analysis. A total of 16 (17.6%) of the 91 patients with NMIBC had tumor recurrences with a median follow-up of 17 months (range, 2-83 months). We confirmed the effect of the European Organization for Research and Treatment of Cancer (EORTC) risk score for predicting tumor recurrence (p = 0.002, log-rank test). We adjusted for the EORTC score and found that 2 SNPs, NOS3 895G>T (rs1799983) (p = 0.02, HR = 4.32, 95% CI, 1.30-14.39, GT+TT vs. GG) and CBR3 730G>A (rs1056892) (p = 0.04, HR = 2.57, 95% CI, 1.07-6.18, GA+AA vs. GG), were significantly associated with a higher recurrence risk after TUR and instillations of THP in NMIBC patients. CONCLUSIONS: Our results suggest that NOS3 895G>T and CBR3 730G>A are genetic markers that can be used to predict tumor recurrence in NMIBC patients receiving intravesical instillations of THP. The effects of those 2 SNPs are independent of the EORTC scores. Further studies with larger sample sizes and longer follow-ups are needed to confirm our results.	bladder
[Clinical application of partial cystectomy with augmentation cystoplasty for invasive bladder cancer in elderly patients].	OBJECTIVE: To evaluate the clinical effect and safety of biological patch applied in elderly patients with invasive bladder cancer who underwent massive partial cystectomy with augmentation cystoplasty. METHODS: The clinical data of 2 patients with invasive bladder cancer from October 2016 to March 2017, who underwent the massive partial cystectomy with augmentation cystoplasty were retrospectively reviewed. Case one was an 87-year-old man, with tumor located on the bladder anterior wall, ranging from 5.5 cm×2.5 cm, and the grade of American Society of Anesthesiologists (ASA) being III. Case two was a 77-year-old female, whose lesion was located on the right anterior wall, ranging from 5.2 cm×4.0 cm, and the grade of ASA being II. Both of the patients received a massive partial cystectomy with augmentation cystoplasty. The operative time, estimated blood loss, perioperative and postoperative data and follow-up data, including cystoscopy and urodynamics were recorded and compared. When the P value was less than 0.05, it was statistically significant. RESULTS: All the operations were successfully performed. The average operative time was (155.0+35.4) min, mean estimated intraoperative blood loss was 20 to 100 mL, and the mean postoperatively hospital stay was eight days. During the 10 to 14 months' follow-up periods, no local recurrence or distant metastasis occurred. Urodynamic data: the maximum urinary flow rate was 16.5 mL/s, and the maximum bladder capacity was 303 mL. The two patients urinated 3-4 times in the day time, 0 to 3 times in the night, 200-300 mL each time, on average. The American Urological Association symptom score was 3 to 5. Partial cystectomy, applied to aged patients with multiple complications and high risk of surgical anesthesia, was able to reduce surgery related complications. For patients with tumor of small size, the normal bladder wall would be enough to recover functional capacity for urine storing after partial cystectomy. For patients with large lesions range and small normal bladder tissues, augmentation cystoplasty would help recover bladder capacity on the condition of negative margin. CONCLUSION: Massive partial cystectomy with augmentation cystoplasty is safe and effective. It could decrease perioperative morbidity and keep the quality-of-life benefits of bladder preservation, which is worthy of further application for some selected invasive bladder cancer in elderly patients.	bladder
FOXM1 overexpression is associated with adverse outcome and predicts response to intravesical instillation therapy in stage pT1 non-muscle-invasive bladder cancer.	OBJECTIVE: To investigate the role of forkhead box protein M1 (FOXM1) mRNA expression and its prognostic value in stage pT1 non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS: Clinical data and formalin-fixed paraffin-embedded tissues from transurethral resection of the bladder from patients with stage pT1 NMIBC, treated with an organ-preserving approach, were analysed retrospectively. Total RNA was isolated using commercial RNA extraction kits, and mRNA expression of FOXM1, MKI67, KRT20 and KRT5 was measured by single-step quantitative RT-PCR using RNA-specific TaqMan Assays. Statistical analysis was performed using Spearman's Rho, Wilcoxon or Kruskal-Wallis tests, Kaplan-Meier estimates of recurrence-free (RFS), progression-free (PFS) and cancer-specific survival (CSS) and Cox regression analysis. RESULTS: Data from 296 patients (79.4% men, median age 72 years) were available for the final evaluation. Spearman correlation analysis showed that mRNA expression of FOXM1 was significantly correlated with MKI67 (ρ: 0.6530, P < 0.001) and with the luminal subtype, reflected by the positive correlation with KRT20 (ρ: 0.2113, P < 0.001). Furthermore, there was also a strong correlation of FOXM1 expression with adverse clinical and pathological variables, such as concomitant carcinoma in situ (P = 0.05), multifocal tumours (P = 0.005) and World Health Organization 1973 grade 3 disease (P < 0.001). Kaplan-Meier analysis showed overexpression of FOMX1 to be associated with worse PFS (P = 0.028) and worse CSS (P = 0.015). FOXM1 overexpression was also shown to be a predictive risk factor for CSS (hazard ratio 1.61 [1.13-2.34], L-R chi-squared: 7.19, P = 0.007). FOXM1 overexpression identified a subgroup of patients within the luminal subtype with worse RFS (P = 0.017), PFS (P < 0.001) and CSS (P = 0.015). Patients with low FOXM1 expression had better outcomes, irrespective of instillation therapy, whereas patients with high FOXM1 expression benefitted from intravesical chemotherapy with mitomycin C. CONCLUSION: High FOXM1 expression was associated with adverse clinical and pathological features and worse outcomes, and predicted response to intravesical instillation therapy in patients with stage pT1 NMIBC.	bladder
The urinary microbiome associated with bladder cancer.	Recent findings suggest that human microbiome can influence the development of cancer, but the role of microorganisms in bladder cancer pathogenesis has not been explored yet. The aim of this study was to characterize and compare the urinary microbiome of bladder cancer patients with those of healthy controls. Bacterial communities present in urine specimens collected from 12 male patients diagnosed with bladder cancer, and from 11 healthy, age-matched individuals were analysed using 16S sequencing. Our results show that the most abundant phylum in both groups was Firmicutes, followed by Actinobacteria, Bacteroidetes and Proteobacteria. While microbial diversity and overall microbiome composition were not significantly different between groups, we could identify operational taxonomic units (OTUs) that were more abundant in either group. Among those that were significantly enriched in the bladder cancer group, we identified an OTU belonging to genus Fusobacterium, a possible protumorigenic pathogen. In an independent sample of 42 bladder cancer tissues, 11 had Fusobacterium nucleatum sequences detected by PCR. Three OTUs from genera Veillonella, Streptococcus and Corynebacterium were more abundant in healthy urines. However, due to the limited number of participants additional studies are needed to determine if urinary microbiome is associated with bladder cancer.	bladder
Long non-coding RNA SNHG20 promotes bladder cancer via activating the Wnt/β-catenin signalling pathway.	The long non‑coding RNA, small nucleolar RNA host gene 20 (SNHG20), is involved in promoting several common types of human cancer, however, the exact function of SNHG20 in the pathogenesis of bladder cancer remains to be elucidated. The present study aimed to examine the regulatory mechanism of SNHG20 underlying the malignant progression of bladder cancer. Reverse transcription‑quantitative polymerase chain reaction and western blotting were used to examine mRNA and protein expression. Cell survival, proliferation, apoptosis, colony formation, migration and invasion were also studied. The resulting data indicated that SNHG20 was significantly upregulated in bladder cancer tissues and cell lines, compared with its expression in adjacent non‑tumour tissues and the SV‑HUC‑1 normal urinary tract epithelial cell line, respectively. In addition, the high expression of SNHG20 was associated with advanced clinical stage, lymph node metastasis, and reduced patient survival rate. The knockdown of SNHG20 caused a significant reduction in cancer cell survival, proliferation, colony formation, migration and invasion, and induced cell apoptosis. Additionally, the inhibition of SNHG20 reduced tumour growth in vivo. Investigations into the mechanism revealed that the inhibition of SNHG20 suppressed the activation of Wnt/β‑catenin signalling and the expression of certain key genes in bladder cancer cells. Taken together, these results indicated that SNHG20 is involved in promoting bladder cancer and may be used as a potential therapeutic target for the treatment of this disease.	bladder
Stability Analysis of Delayed Immune Response BCG Infection in Bladder Cancer Treatment Model by Stochastic Perturbations.	We present a revised mathematical model of the immune response to Bacillus Calmette-Guérin (BCG) treatment of bladder cancer, optimized according to biological and clinical data accumulated during the last decade. The improved model accounts for cytotoxic T lymphocyte differentiation as an integral element of the delayed immune response, as well as the logistic growth terms for cancer cell proliferation. Three equilibria are demonstrated for the proposed model, which is assumed to be influenced by white noise stochastic perturbations that are directly proportional to the system state deviation from an equilibrium. Stability conditions for all equilibria are analyzed using the Kolmanovskii-Shaikhet general method of Lyapunov functionals construction.	bladder
Pelvic lymph node dissection during radical cystectomy for muscle-invasive bladder cancer.	Radical cystectomy is the gold-standard treatment option for muscle-invasive and metastatic bladder cancer. At the time of cystectomy, up to 25% of patients harbour metastatic lymph node deposits. These deposits most frequently occur in the obturator fossa, but can be as proximal as the interaortocaval region. Thus, the use of concurrent pelvic lymph node dissection (PLND) with cystectomy has been increasingly reported. Data from studies including many patients suggest substantial oncological benefit in PLND cohorts versus non-PLND cohorts, irrespective of pathological nodal status. Additionally, PLND provides useful prognostic information, including disease burden, lymph node density, and extracapsular extension of metastatic lymph nodes. Accordingly, the National Comprehensive Cancer Network guidelines advocate the use of PLND during radical cystectomy for muscle-invasive bladder cancer. Despite this recommendation, a lack of consensus exists regarding the optimal PLND template. Comparative series suggest that extended PLND provides improved recurrence-free survival and cancer-specific survival compared with more limited PLND templates. More extensive templates (such as super-extended PLND) provide no additional survival benefit at the potential cost of increased operative time and patient morbidity. In addition to extended PLND templates, increased nodal harvest confers an oncological benefit in patients with node-positive disease or in patients with node-negative disease. Accordingly, recommendations for a minimum nodal yield have been proposed. Despite the growing body of evidence, formal recommendations by oncological and urological authoritative bodies have been limited owing to the lack of randomized data and level I evidence.	bladder
Decreased c-Myc mRNA Stability via the MicroRNA 141-3p/AUF1 Axis Is Crucial for p63α Inhibition of Cyclin D1 Gene Transcription and Bladder Cancer Cell Tumorigenicity.	"Bladder cancer (BC) ranks as the sixth most common cancer in the United States and is the leading cause of death in patients with urinary malignancies. p63 is a member of the p53 family and is believed to function as a tumor suppressor in human BCs. Our most recent studies revealed a previously unknown function of the RING of XIAP in promoting microRNA 4295 (miR-4295) transcription, thereby reducing p63α protein translation and enhancing normal urothelial transformation, whereas p63α upregulates hsp70 transcription, subsequently activating the HSP70/Wasf3/Wave3/matrix metalloproteinase 9 (MMP-9) axis and promoting BC cell invasion via initiating the transcription factor E2F1. In this study, we found that p63α inhibited cyclin D1 protein expression, subsequently decreasing the ability of BC cell anchorage-independent growth in vitro and tumorigenicity in vivo Mechanistic studies demonstrated that p63α expression is able to downregulate cyclin D1 gene transcription through attenuation of c-Myc mRNA stability. We further show that the reduction of miR-141-3p expression by p63α directly releases its inhibition of 3' untranslated region (UTR) activity of AU-rich element RNA-binding factor 1 (AUF1) mRNA, thereby increasing AUF1 protein translation and further resulting in degradation of c-Myc mRNA, which, in turn, reduces cyclin D1 gene transcription and BC cell anchorage-independent growth. Collectively, our results demonstrate that p63α is a negative regulator of BC cell tumorigenic growth, a distinctly different function than its promotion of BC invasion, thus providing further new insight into the ""two faces"" of p63α in regulation of BC cell tumorigenic growth and progression/invasion."	bladder
Mediterranean Diet and Bladder Cancer Risk in Italy.	Previous studies have reported that Mediterranean diet is inversely related to the risk of several neoplasms; however, limited epidemiological data are available for bladder cancer. Thus, we examined the association between Mediterranean diet and this neoplasm in an Italian multicentric case-control study consisting of 690 bladder cancer cases and 665 controls. We assessed the adherence to the Mediterranean diet via a Mediterranean Diet Score (MDS), which represents the major characteristics of the Mediterranean diet and ranges from 0 to 9 (from minimal to maximal adherence, respectively). We derived odds ratios (ORs) of bladder cancer according to the MDS score from multiple logistic regression models, allowing for major confounding factors. The ORs of bladder cancer were 0.72 (95% confidence interval, CI, 0.54⁻0.98) for MDS of 4⁻5 and 0.66 (95% CI, 0.47⁻0.93) for MDS of 6⁻9 (p for trend = 0.02) compared to MDS = 0⁻3. Results were similar in strata of sex, age, and education, while the risk appeared somewhat lower in never-smokers and patients with pT1⁻pT4 bladder carcinomas. Among individual components of the MDS, we observed inverse associations for greater consumption of legumes, vegetables, and fish. In our study, which was carried out on an Italian population, the higher adherence to the Mediterranean diet was related to a lower risk of bladder cancer.	bladder
[Practice Pattern of Systemic Therapy for Urothelial Cancer in Germany - A Survey of the German Cancer Society].	BACKGROUND:  In 2016, the first German guideline for bladder cancer was introduced. This survey evaluates current management of bladder cancer in Germany, focusing on systemic therapies and compares this to the guidelines. MATERIAL AND METHODS:  More than 4000 urologists and oncologists in Germany received a questionnaire assessing surgical and systemic therapeutic management of bladder cancer. We received 278 evaluable responses. RESULTS:  This is the largest nationwide survey evaluating current bladder cancer management in Germany. Management can be optimised of non-muscle invasive bladder cancer including intravesical instillation therapies, as well as of muscle invasive bladder cancer including (neo)adjuvant chemotherapies, particularly with respect to the numbers of chemotherapy courses. Management of metastasised bladder cancer is predominantly performed according to the guidelines. CONCLUSIONS:  Adherence to bladder cancer guidelines in Germany can be optimised and could possibly decrease cancer-specific mortality, supported by the development of novel diagnostic and therapeutic options.	bladder
Age at Exposure to Arsenic in Water and Mortality 30-40 Years After Exposure Cessation.	Arsenic in drinking water is known to cause cancer and noncancer diseases, but little is known about its association with age at exposure. Here, we investigated age at arsenic exposure and mortality in Antofagasta, Chile, 30-40 years after a distinct period of very high water arsenic concentrations (1958-1970). We calculated standardized mortality ratios (SMRs) comparing Antofagasta with the rest of Chile for 2001-2010 by sex and age at potential first exposure. A remarkable relationship with age at first exposure was found for bronchiectasis, with increased risk in adults 30-40 years after exposure being confined to those who were in utero (SMR = 11.7, 95% confidence interval (CI): 4.3, 25.4) or aged 1-10 years (SMR = 5.4, 95% CI: 1.1, 15.8) during the high-exposure period. Increased SMRs for lung, bladder, and laryngeal cancer were evident for exposures starting at all ages, but the highest SMRs were for exposures beginning at birth (for bladder cancer, SMR = 16.0 (95% CI: 10.3, 23.8); for laryngeal cancer, SMR = 6.8 (95% CI: 2.2, 15.8); for lung cancer, SMR = 3.8 (95% CI: 2.9, 4.9)). These findings suggest that interventions targeting early-life arsenic exposure could have major impacts in reducing long-term mortality due to arsenic 30-40 years after exposure ends.	bladder
The clinical applications of The Cancer Genome Atlas project for bladder cancer.	Knowledge of the molecular subtypes of bladder cancer enables powerful generalizations involving the distinctive biology and pathways driving different disease subsets. Areas covered: In this review, we summarize the findings of a number of published studies exploring the molecular landscape of bladder cancer by analysis of genomic data from The Cancer Genome Atlas (TCGA). TCGA project has provided a comprehensive data resource of 412 muscle-invasive bladder cancers as characterized by multiple molecular analytical platforms. These data have been and will continue to be utilized in numerous subsequent studies aimed at better understanding the molecular basis of bladder cancer. The catalog of DNA-level alterations can greatly inform personalized and precision medicine approaches. Molecular subtypes of bladder cancer include distinct 'basal/squamous' and 'luminal' subtypes, cancers with papillary histology, disease subsets with prominent leukocyte infiltration and immune checkpoint marker expression, and a 'neuronal' subtype lacking small cell or neuroendocrine histology. The gene-level alterations and subtypes as revealed by TCGA data are relevant from the standpoint of both basic biology and clinical trial studies. Expert commentary: Multiple studies analyzing TCGA muscle-invasive bladder cancer cases point to the existence of five major expression-based molecular subtypes of the disease, with these subtypes having therapeutic implications.	bladder
Ureteral pseudodiverticulosis and urothelial cell carcinoma: rethinking the association.	PURPOSE: To compare frequency of new and recurrent urothelial cell carcinoma (UCC) among patients with and without pseudodiverticulosis on imaging. METHODS: This retrospective case-control study compared all 113 sequential patients with ureteral pseudodiverticulosis on radiographic urography between 1/1/2002 and 12/31/2012. Six patients were lost to follow-up. 107 patients without pseudodiverticulosis were matched by imaging modality, clinical indication, and tumor grade. Known UCC and primary outcome of new or recurrent UCC were determined through pathology on cystoscopy or clinical follow-up. RESULTS: Nearly half of patients with pseudodiverticulosis had known UCC at the time of imaging (49/107, 46%). Mean cystoscopy follow-up was 7.0 and 4.6 years for pseudodiverticulosis cases with and without known UCC, respectively, and 7.5 and 7.3 years for controls, respectively. Mean clinic follow-up was 7.5 and 6.0 years for pseudodiverticulosis cases with and without known UCC, respectively, and 6.4 and 7.6 years for controls, respectively. Among patients with known UCC at the time of imaging, similar rates of recurrent UCC were demonstrated on follow-up among patients with pseudodiverticulosis (6/49, 12%) and without (7/49, 14%). Among patients with no known history of UCC at the time of imaging, no patients with pseudodiverticulosis developed UCC on follow-up and 5% (3/58) of patients without pseudodiverticulosis developed UCC. CONCLUSION: Although half of patients with ureteral pseudodiverticulosis have a known diagnosis of UCC, the presence of pseudodiverticulosis did not signify an increased likelihood of developing new or recurrent UCC over the follow-up period.	bladder
LncRNA PVT1 regulates VEGFC through inhibiting miR-128 in bladder cancer cells.	Long noncoding RNA PVT1 is considered to be an oncogene in multiple cancers. Our previous studies indicated that PVT1 levels were higher in bladder cancer tissue and correlated with clinical progression and poor prognosis in bladder cancer patients. A bioinformatics analysis showed that PVT1 may regulate VEGFC expression through miR-128 as a competing endogenous RNA (ceRNA). In this study, we demonstrated that PVT1 expression levels affect the proliferation and migration ability of bladder cancer cells. Moreover, PVT1 knockdown significantly decreased the proliferation capacity of bladder cancer cells in nude mice. Luciferase assays and RNA-binding protein immunoprecipitation were performed to investigate the potential mechanism of ceRNAs in the regulation of PVT1 and VEGFC. The results showed that the increased number of PVT1 transcripts interacted directly with miR-128 to decrease miR-128 binding to the VEGFC 3'-untranslated region. This effect suppressed VEGFC mRNA degradation by miR-128. In conclusion, these results indicated that PVT1 might play a critical role in bladder cancer tumorigenesis via miR-218 and VEGFC. Therefore, PVT1 could be a new biomarker for bladder cancer diagnosis and therapy.	bladder